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Glycolysis = breakdown of sugars; glycogen, glucose, fructose

Glycolysis = breakdown of sugars; glycogen, glucose, fructose. Where in body? Where in cell? What are the inputs? What are the outcomes?. Oxygen required?. Gibbs Free Energy Changes Rxn# Enzyme D G°'(kJ/mol) D G(kJ/mol) 1 Hexokinase -16.7 -33.5 Phosphogluco-isomerase +1.7 -2.5

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Glycolysis = breakdown of sugars; glycogen, glucose, fructose

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  1. Glycolysis = breakdown of sugars; glycogen, glucose, fructose Where in body? Where in cell? What are the inputs? What are the outcomes? Oxygen required?

  2. Gibbs Free Energy Changes • Rxn# Enzyme DG°'(kJ/mol) DG(kJ/mol) • 1 Hexokinase -16.7 -33.5 • Phosphogluco-isomerase +1.7 -2.5 • 3 Phosphofructokinase -14.2 -22.2 • 4 Aldolase +23.9 -1.3 • 5 Triose phos. Isomerase +7.6 +2.5 • 6 G-3-PDH +12.6 -3.4 • 7 Phosphoglycerate kinase -37.6 +2.6 • 8 Phosphoglycerate mutas +8.8 +1.6 • 9 Enolase +3.4 -6.6 • 10 Pyruvate kinase -62.8 -33.4 1 1 2 3 4 5 Identify: endergonic rxns exergonic rxns coupled reactions oxidation/reduction rxns transfer reactions 6 7 8 9 10

  3. When do we use glycolysis? What are the advantages of using glycolysis for energy supply? What are the disadvantages? How is glycolysis regulated?

  4. Hexokinase inhibited by glucose –6-phosphate; also there are several isoforms; lowest Km in liver Phosphofructokinase (PFK) (+) (-) Pyruvate kinase inhibited by ATP and acetylCoA; activated by fructose 1,6 bisphosphate

  5. Where do the intermediates in glycolysis go? • G-6-P goes off to make the ribose for nucleotides • F-6-P -amino sugars-glycolipids and glycoproteins • G-3-P/DHAP-lipids • 3PG-serine • PEP-aromatic amino acids, pyrimidines, asp and asn • Pyruvate-alanine • This pathway not only important in glucose metabolism--generates intermediates for other important building blocksG-6-P = glucose 6 phosphate, F-6-P = fructose 6 phosphate, G-3-P = glyceraldehyde 3 phosphate, DHAP = dihydryoxacetonephosphate, 3PG = phosphoglyceraldehyde, Pyr = pyruvate

  6. What are the possible fates of pyruvate? • Ethanol (fermentation) • Acetyl coA (mammals and others) • TCA/Krebs cycle • Oxaloacetate - gluconeogenesis • Lactate (mammals and others) • End product of anaerobic glycolysis • Gluconeogenesis in liver via the Cori cycle

  7. Cori cycle oxaloacetate

  8. Cori Cycle

  9. Net Gain: + 2 ATP Energy Balance Sheet for the Oxydation of Glucose via Glycolysis Gains: 4 ATP 2 pyruvate 2 NADH + H+ Losses: 2ATP Glucose Phosphate NAD+ (recycled) Mitochondria for further oxidation via the TCA/Krebs cycle

  10. Oxidation of pyruvate via the TCA/Krebs/Citric Acid Cycle

  11. Pyruvate CO2 NAD+ NADH Acetyl CoA • All compounds are tricarboxylic acids • Carbons from glucose are shown in red • Carbons from glucose are lost as CO2 (decarboxylation) • Several NADH + H+ are generated via oxidation of intermediates • One high energy phosphate compound (GTP)is produced

  12. When do we oxidize pyruvate via the Krebs cycle? What do we need to accomplish the oxidation of pyruvate? • NAD+ and FAD+; each can carry 2 e- • oxygen; needs 2 e- to fill outer valence shell of electrons • glucose Where are the Krebs cycle enzymes and electron transport proteins located? • Krebs cycle enzymes are located in the mitochondrial matrix • Electron transport proteins in the inner mitochondrial membrane

  13. Prosthetic groups = Fe, Flavin, Fe-S, Cu Coenzyme Q (ubiquinone) Cytochrome c Complex I = NADH ubiquinone oxidoreductase Complex II = succinate-ubiquinone oxidoreductase Complex III = cytochrome c oxidoreductase

  14. Electron transport proteins each can accept or give up two electrons one protein in each complex also acts as a hydrogen pump electron entry point is determined by the energy state of the electrons

  15. Pyruvate CO2 NAD+ NADH Acetyl CoA

  16. Entry point for electrons carried by FADH2 Entry point for electrons carried by NADH+ H+

  17. Net Energy Yield from the Oxidation of Pyruvate via the TCA cycle From Glycolysis: +2NADH +2ATP From TCA: +2FADH +8NADH +2GTP ETC: 3ATP/NADH 2ATP/FADH +4ATP +30ATP +38ATP TOTAL + + Do you know why?

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